Simultaneous Herpetic and Candidal Esophagitis in an Immunocompetent Teenager

Abstract

INTRODUCTION Infection is an uncommon cause of esophagitis in children. Common pathogens causing esophagitis include Candida spp. and Herpes simplex virus (HSV). Infectious esophagitis is generally seen in immunocompromised patients but has been rarely reported in healthy individuals. Esophagitis with evidence of both Candida spp. and HSV has not been reported previously in immunocompetent children. We report a case of a healthy teenager with both pathogens causing esophageal infection. CASE REPORT A 15-year-old previously healthy male presented with a 5-day history of progressive dysphagia and odynophagia. He had fever, vomiting and diarrhea for 2 days. He had no previous hospitalizations. He underwent insertion of tympanostomy tubes in childhood but had no other surgeries. He had no history of recurrent infections or other findings suggestive of immunodeficiency. He denied sexual activity or illicit drug use. His only medications were bupropion for depression, methylphenidate for attention deficit disorder and inhaled albuterol as required for mild asthma. He had not required any oral or inhaled steroid therapy for his asthma or for any other indication. On admission, he was uncomfortable and complained of mild midsternal chest pain. His vital signs and physical examination were normal. His weight and height percentiles were >97% and 94%, respectively. He had normal serum electrolytes, amylase, lipase and immunoglobulin levels. His complete blood count showed a platelet count of 249,000/mm3, hemoglobin 14.2 g/dL and a white blood cell count of 9900/mm3 with 12% lymphocytes and 73% neutrophils. His C-reactive protein was 10.8 mg/dL (normal <0.5 mg/dL). Upper endoscopy revealed several white patches and exudates throughout the esophagus with an edematous friable mucosa suggestive of severe candidal esophagitis. Except for mild gastric mucosal erythema, the endoscopy was otherwise normal. Microscopic examination of the esophageal biopsies showed several multinucleated squamous cells. Fungal forms were also identified. Culture of his mucosal biopsy specimens grew HSV type I. Potassium hydroxide smear showed yeast. Oral fluconazole and lansoprazole were started for the presumptive diagnosis of candidal esophagitis and the patient was discharged home. Because of worsening odynophagia and the inability even to swallow medications, he was re-admitted the next day for inpatient management and intravenous hydration. Once culture results were available, intravenous fluconazole, acyclovir and famotidine were initiated. Intravenous morphine drip and oral analgesics were given for pain control. Intravenous hydration and pain medications were gradually discontinued over 5 days at which time he was discharged. At the time of discharge, he was tolerating oral intake well. He was scheduled to complete 14 days of fluconazole and acyclovir at home. Seven months later, the patient continued to be symptom-free without any evidence of recurrence or any major medical illnesses or infections. DISCUSSION We report an apparently immunocompetent young patient with infectious esophagitis. Although immunologic testing was by no means complete in our case, his previous unremarkable history, rapid recovery, normal laboratory evaluations and absence of recurrence makes the possibility of an underlying immunodeficiency, such as human immunodeficiency virus infection, extremely unlikely. Our patient's endoscopic appearance was highly suggestive of a candidal infection, but histologic evidence of both Candida spp. and HSV type I was obtained. Common causes of esophagitis in children include reflux and allergy. Infections of the esophagus are rare and most commonly seen in immunocompromised individuals. Common infectious agents include Candida spp., HSV and cytomegalovirus (1-2). Immunosuppression is one of the main predisposing factors for both HSV and candidal esophagitis. Patients with cancer or defects of cellular immunity such as acquired immunodeficiency syndrome and those receiving chemotherapy, radiotherapy or corticosteroid treatment are at particular risk. Other predisposing factors include broad spectrum antibiotic therapy, diabetes and blood dyscrasias (3-4). Use of proton pump inhibitors has been implicated as a contributor to the development of candidal esophagitis (3). Candidal esophagitis can also affect healthy children. HSV is also rarely reported as a cause of esophagitis in otherwise healthy pediatric patients (2,5-6). Simultaneous esophageal infection with HSV and Candida spp. is rare. A few cases have been described, mainly in adults with sepsis or malignancies receiving radiation or chemotherapy (7-10). Hemstreet et al. described the only pediatric case of esophagitis associated with two pathogens (11). This was a report of a 13-year-old male on prolonged inhaled steroid therapy and repeated oral steroid courses who developed dual esophageal infection. Immunosuppression resulting from chronic steroid use was implicated in the development of this co-infection. The authors hypothesized that the patient developed primary HSV gingivostomatitis with secondary esophageal infection from the swallowed virus. Esophageal infection with Candida sp. might have occurred in a similar fashion or as a superinfection (11). Reports in adults with dual esophageal infections presumed that a possible mechanism includes injury to the esophageal epithelium by HSV first and disruption of the mucosal barrier creating a supportive environment for Candida spp.(10). As in our patient, infectious esophagitis usually presents with an acute onset of symptoms as opposed to the more gradual course in patients with reflux or eosinophilic esophagitis. Odynophagia, dysphagia, retrosternal chest pain, vomiting and fever are the usual manifestations of infectious esophagitis. It is usually not possible to distinguish herpes from candidal esophagitis from symptoms alone (2-3,12-13). The presence of oral thrush or herpetic vesicles may give clues to the diagnosis (10). Endoscopy with biopsies for culture and histologic studies remains the best diagnostic test. Herpetic lesions of the esophagus usually begin with vesicle formation, followed by punched-out ulcer formation. They are commonly seen as discrete ulcerations on an inflamed and friable mucosa at endoscopy. The heaped-up borders of herpetic ulcers result in the classic “volcano lesions.” The distal esophagus is usually more affected than the proximal esophagus (2,14). In candidal esophagitis, the esophageal mucosa is typically friable and erythematous with ulcers covered by thick adherent white exudate (14). Histologic demonstration of intranuclear inclusions in epithelial cells or multinucleated giant cells with ground glass appearing nuclei is occasionally found in the biopsies of patients with herpes esophagitis (7,9,14). Ideally, to confirm the presence of invasive candidal esophagitis, Candida spp. are seen along with squamous cells and invading hyphae on smears (4,14). Herpes esophagitis is usually regarded as a self-limited illness in otherwise healthy individuals. Symptoms typically resolve in 2 to 20 days with supportive care. Symptomatic therapy with intravenous hydration and analgesics is often required. Treatment with acyclovir is recommended in severe cases and in immunocompromised patients (2,5). Antifungal agents used in esophageal candidiasis treatment include nystatin, fluconazole, flucytosine, itraconazole and amphotericin B (4,12-13). The choice of agent depends on the immune status of the patient and the extent of the disease. Nystatin has little efficacy in immunosuppressed patients. Fluconazole therapy for 14 days is usually well tolerated and effective for candidal esophagitis. In severe dual infection, as seen in our patient, use of both antiviral and antifungal agents may be required. Concomitant infection of the esophagus with herpes and candida is rare and is most commonly seen in the immunosuppressed or the elderly. Rarely, it may occur in healthy young immunocompetent individuals such as our patient. Endoscopy to obtain biopsies for histology and culture is the best way to determine the cause of infection and choose the appropriate antimicrobial therapy. In severe cases of esophagitis with two organisms, therapy against both pathogens is recommended.